SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03919071

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase 2 Study of Dabrafenib (NSC# 763760) With Trametinib (NSC# 763093) After Local Irradiation in Newly-Diagnosed BRAF V600-Mutant High-Grade Glioma (HGG)

This phase II trial studies how well dabrafenib with trametinib work after radiation therapy in treating patients with a type of genetic mutation (BRAF V600-mutant) and newly-diagnosed, high-grade glioma. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving dabrafenib with trametinib after radiation therapy may work better than treatments used in the past in helping to get rid of or shrinking tumors in patients with newly-diagnosed BRAF V600-mutant high-grade glioma.

NCT03919071 Anaplastic Astrocytoma Anaplastic Ganglioglioma Anaplastic Pleomorphic Xanthoastrocytoma BRAF NP_004324.2:p.V600X Glioblastoma H3 K27M Negative Malignant Glioma WHO Grade III Glioma
MeSH: Glioblastoma Glioma Astrocytoma Ganglioglioma
HPO: Astrocytoma Glioblastoma multiforme Glioma Subependymal giant-cell astrocytoma

5 Interventions

Name: Dabrafenib

Description: Given PO

Type: Drug

Treatment (radiation therapy, dabrafenib, trametinib)

Name: Dabrafenib Mesylate

Description: Given PO

Type: Drug

Treatment (radiation therapy, dabrafenib, trametinib)

Name: Radiation Therapy

Description: Undergo RT

Type: Radiation

Treatment (radiation therapy, dabrafenib, trametinib)

Name: Trametinib

Description: Given PO

Type: Drug

Treatment (radiation therapy, dabrafenib, trametinib)

Name: Trametinib Dimethyl Sulfoxide

Description: Given PO

Type: Drug

Treatment (radiation therapy, dabrafenib, trametinib)


Primary Outcomes

Description: The EFS curve for the new treatment cohort (Stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the EFS distribution is better in new treatment compared with historical control. Calculation of the EFS will be based on the site determination as central review will be performed retrospectively.

Measure: Event-free survival (EFS)

Time: From the date of diagnosis until disease progression date, secondary malignant neoplasm occurrence date, death date of any cause, or last follow-up, assessed up to 5 years

Secondary Outcomes

Description: The OS curve for the new treatment cohort (Stratum 1) will be estimated by Kaplan Meier estimates. A 2-sample, 1 sided log-rank test will be used to test whether the OS distribution is better in new treatment compared with historical control.

Measure: Overall survival (OS)

Time: From the date of diagnosis until death date of any cause or last follow up date, assessed up to 5 years

Description: Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Grade 3 and higher toxicities observed by cycle will be listed for each stratum separately. The grade 3 and higher toxicities observed by cycle and by system organ class for the eligible patients will also be listed for each stratum separately. Toxicity data will be reported separately for the radiation therapy phase versus the maintenance therapy phase for clarity of attribution. Toxicity monitoring will include toxicities such as grade 2 or higher pyrexia, uveitis, retinal vein occlusion, retinal pigment epithelial detachment, and decreased left ventricular ejection fraction.

Measure: Incidence of adverse events

Time: Up to 5 years

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 K27M

- Patients must have eligibility confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 - Newly diagnosed high-grade glioma with BRAFV600-mutation - Negative results for H3 K27M by immunohistochemistry (IHC) - Histologically confirmed high-grade glioma (World Health Organization [WHO] grade III or IV) including but not limited to: anaplastic astrocytoma (AA), anaplastic pleomorphic xanthoastrocytoma (aPXA), anaplastic gangliogliomas (aGG), glioblastoma (GB), and high-grade astrocytoma, not otherwise specified (NOS) - Patients must have had histologic verification of a high-grade glioma diagnosis. --- K27M ---

Anaplastic Astrocytoma Anaplastic Ganglioglioma Anaplastic Pleomorphic Xanthoastrocytoma BRAF NP_004324.2:p.V600X Glioblastoma H3 K27M Negative Malignant Glioma WHO Grade III Glioma Glioblastoma Glioma Astrocytoma Ganglioglioma PRIMARY OBJECTIVES: I. To estimate the event-free survival (EFS) distribution for newly-diagnosed patients with BRAFV600-mutant high-grade glioma (HGG) without H3 K27M mutations excluding anaplastic pleomorphic xanthoastrocytoma (aPXA) and anaplastic ganglioglioma (aGG) treated with radiation therapy followed by a maintenance combination of dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) and to compare this EFS to contemporary historical controls. --- K27M ---

Anaplastic Astrocytoma Anaplastic Ganglioglioma Anaplastic Pleomorphic Xanthoastrocytoma BRAF NP_004324.2:p.V600X Glioblastoma H3 K27M Negative Malignant Glioma WHO Grade III Glioma Glioblastoma Glioma Astrocytoma Ganglioglioma PRIMARY OBJECTIVES: I. To estimate the event-free survival (EFS) distribution for newly-diagnosed patients with BRAFV600-mutant high-grade glioma (HGG) without H3 K27M mutations excluding anaplastic pleomorphic xanthoastrocytoma (aPXA) and anaplastic ganglioglioma (aGG) treated with radiation therapy followed by a maintenance combination of dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) and to compare this EFS to contemporary historical controls. --- K27M --- --- K27M ---

SECONDARY OBJECTIVES: I. To describe the overall survival (OS) distribution for newly-diagnosed patients with BRAFV600-mutant HGG without H3 K27M mutations excluding aPXA and aGG treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib. --- K27M ---

To describe the EFS and overall survival (OS) distribution for newly-diagnosed patients with BRAFV600E-mutant aPXA and aGG without H3 K27M mutations treated with radiation therapy followed by a maintenance combination of dabrafenib and trametinib. --- K27M ---



HPO Nodes


HPO:
Astrocytoma
Genes 14
NF2 APC MLH1 CDKN2A MSH6 ERBB2 TSC1 TSC2 PMS2 MSH2 MSH3 IDH1 IDH2 NF1
Glioblastoma multiforme
Genes 16
PMS1 APC MLH1 KRAS EPCAM TGFBR2 PIK3CA MSH6 ERBB2 RPS20 BMPR1A PMS2 MSH2 MLH3 SEMA4A FAN1
Glioma
Genes 30
CHEK2 PMS1 APC MLH1 CDKN2A KRAS TGFBR2 LRP5 NBN MSH6 C11ORF95 ERBB2 RPS20 TSC1 BMPR1A TSC2 RELA PMS2 MSH2 MSH3 MLH3 IDH1 IDH2 SEMA4A NF1 NF2 EPCAM PIK3CA SETBP1 FAN1
Subependymal giant-cell astrocytoma
Genes 2
TSC1 TSC2